Saxagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus

Edelman, Steve

doi:10.2147/ce.s8006

Cited by 12 publications

(11 citation statements)

References 33 publications

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“…Reseptor yang digunakan adalah DPP-4 (PDB: 3CCB). Adapun kontrol yang digunakan adalah Saxagliptin (PDB: 3W2T) yang dapat menurunkan ekspresi DPP-4 dengan 10 kali lipat lebih besar dibandingkan dengan sitagliptin dan vildagliptin meskipun secara klinis efek ketiganya hampir sama (Kulasa dan Edelman, 2010). Berikut ini merupakan gambar struktur molekular dari senyawa Molekular Docking.…”

Section: Metode Penelitianunclassified

“…Saxagliptin merupakan obat inhibitor DPP-4 pada diabetes mellitus dan terbukti memiliki beberapa aktivitas di antaranya menurunkan hemoglobin terikat glukosa (HbAIc) dan glukosa plasma puasa, memperbaiki fungsi sel β-pankreas, meningkatkan postprandial insulin, menurunkan postprandial glukagon, dengan resiko hypoglikemia dan penyakit kardiovaskular yang rendah. Saxagliptin memiliki kemampuan berikatan dengan sisi aktif dan kemampuan menghambat DPP-4 10 kali lipat lebih besar dibandingkan dengan sitagliptin dan vildagliptin meskipun secara klinis efek ketiganya hampir sama (Kulasa dan Edelman, 2010).…”

Section: Pembahasanunclassified

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STUDI IN SILICO POTENSI SENYAWA ALLIIN BAWANG PUTIH (Allium sativum) SEBAGAI INHIBITOR DPP-4 PADA DIABETES MELLITUS

Rohmah

2018

JINTO

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Diabetes mellitus (DM) merupakan penyakit gangguan metabolisme glukosa yang dicirikan dengan gangguan sekresi dan resistensi insulin. Jalur pengobatan DM baru pada sistem increatin dengan penghambatan terhadap DPP-4 telah dikembangkan dan terbukti efektif untuk meningkatkan sekresi insulin, menjaga integritas sel β-pankreas, memperlambat pengosongan lambung dan meningkatkan lipogenesis tanpa menyebabkan efek samping sistemik. Bawang putih (Allium sativum) diketahui memiliki aktivitas antidiabetes di antaranya meningkatkan sekresi insulin dan menurunkan level glukosa plasma, memiliki aktivitas insulinotropik dibandingkan dengan hypoglikemik. Namun demikian mekanisme molekuler dari aktivitas ini belum banyak diketahui. Penelitian ini bertujuan untuk mengetahui potensi senyawa Alliin pada bawang putih (Allium sativum) sebagai inhibitor DPP-4 secara in silico menggunakan metode docking server. Hasil penelitian ini menunjukkan bahwa, senyawa Alliin terbukti dapat berikatan kuat dengan DPP-4 dengan interaksi permukaan sebesar 120.032. Ikatan Alliin dan DPP-4 sangat stabil dibuktikan dengan energi ikatan bebas yang kecil (-0.59 kcal/mol). Alliin juga terbukti memiliki aktivitas penghambatan pada DPP-4 inhibitor dibuktikan nilai konstanta inhibisi (Ki) yaitu 792.92 mM. Hal ini didukung oleh adanya kesamaan struktur antara ikatan rangkap O (=O) dan NH2 antara alliin dengan saxagliptin. Penelitian ini membuktikan bahwa senyawa Alliin dapat berikatan dengan DPP-4 dan mampu memberikan efek penghambatan.

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Section: Metode Penelitianunclassified

Section: Pembahasanunclassified

STUDI IN SILICO POTENSI SENYAWA ALLIIN BAWANG PUTIH (Allium sativum) SEBAGAI INHIBITOR DPP-4 PADA DIABETES MELLITUS

Rohmah

2018

JINTO

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“…[ 16 ] The results from the pooled analysis of the monotherapy study, as well as the initial combination and add-on therapy studies, concluded that saxagliptin had a low risk of hypoglycemia when used as a monotherapy or in combination with metformin, SUs, or TZDs. [ 1 ] Ability of saxagliptin to lower HbA 1C without increasing hypoglycemic episodes is due to its glucose-dependent action and is one of the main advantages as compared with other insulin secretagogues such as SUs. [ 21 ] Contrary to SUs and TZDs, saxagliptin monotherapy has a weight-neutral effect.…”

Section: Clinical Pharmacology Of Saxagliptinmentioning

confidence: 99%

“…Diabetes has an estimated prevalence of around 220 million people worldwide and it is estimated to affect around 440 million by 2030. [ 1 ] Of these, around 90 to 95% of cases are of T2DM. [ 1 ] Expected rise in prevalence of diabetes is mainly due to increased life span because of better healthcare facilities and increase in diabetic risk factors, especially physical inactivity and obesity due to sedentary life style.…”

Section: Introductionmentioning

confidence: 99%

“…[ 1 ] Of these, around 90 to 95% of cases are of T2DM. [ 1 ] Expected rise in prevalence of diabetes is mainly due to increased life span because of better healthcare facilities and increase in diabetic risk factors, especially physical inactivity and obesity due to sedentary life style. [ 2 ] Pancreatic β-cell function is gradually deteriorated in patients of T2DM which is reflected into inadequate glycemic control on a long run.…”

Section: Introductionmentioning

confidence: 99%

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Saxagliptin: A dipeptidyl peptidase-4 inhibitor in the treatment of type 2 diabetes mellitus

Dave¹

2011

Journal of Pharmacology and Pharmacotherapeutics

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Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by insulin deficiency or resistance. Management starts with single oral antidiabetic drug (OAD) but eventually switch over to combination therapy because of progressive β-cell dysfunction. Hypoglycemia, weight gain, and adverse cardiovascular events are major limitations of the available OADs (Sulfonylureas [SUs], thiazolidinediones [TZDs]). Saxagliptin, a reversible, competitive dipeptidyl peptidase-4 inhibitor, is recently approved agent in the treatment of T2DM. It acts by preventing the degradation of glucagon-like peptide – 1 and hence increases secretion of insulin and decreases secretion of glucagon. It is a well-tolerated agent with commonly reported adverse events which include upper respiratory tract infection, urinary tract infection, and headache. Hypoglycemia, weight gain, and adverse cardiovascular events are negligible as compared with other OADs. In clinical studies, saxagliptin was found to be effective and well tolerated when used as a monotherapy as well as in combination with metformin, SUs and TZDs. It is administered in the dose range of 2.5 to 5 mg once a day regardless of meal. Dosage reduction is required in patients having moderate to severe renal impairment as well as with concurrent administration of strong CYP3A4/5 inhibitors. To conclude, saxagliptin because of its novel mechanism of action (preserving beta cell function) and better tolerability profile seems to be a promising agent in the treatment of T2DM, especially in the early stage of the disease, but long-term clinical studies are required to prove its status in the management of T2DM.

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Clinical Pharmacokinetics and Pharmacodynamics of Saxagliptin, a Dipeptidyl Peptidase-4 Inhibitor

Boulton

2016

Clin Pharmacokinet

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Saxagliptin is an orally active, highly potent, selective and competitive dipeptidyl peptidase (DPP)-4 inhibitor used in the treatment of type 2 diabetes mellitus at doses of 2.5 or 5 mg once daily. DPP-4 is responsible for degrading the intestinally derived hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP). Inhibition of DPP-4 increases intact plasma GLP-1 and GIP concentrations, augmenting glucose-dependent insulin secretion. Both saxagliptin and its major active metabolite, 5-hydroxy saxagliptin, demonstrate high degrees of selectivity for DPP-4 compared with other DPP enzymes. Saxagliptin is orally absorbed and can be administered with or without food. The half-life of plasma DPP-4 inhibition with saxagliptin 5 mg is ~27 h, which supports a once-daily dosing regimen. Saxagliptin is metabolized by cytochrome P450 (CYP) 3A4/5 and is eliminated by a combination of renal and hepatic clearance. No clinically meaningful differences in saxagliptin or 5-hydroxy saxagliptin pharmacokinetics have been detected in patients with hepatic impairment. No clinically meaningful differences in saxagliptin or 5-hydroxy saxagliptin pharmacokinetics have been detected in patients with mild renal impairment, whereas dose reduction is recommended in patients with moderate or severe renal impairment because of greater systemic exposure [the area under the plasma concentration-time curve (AUC)] to saxagliptin total active moieties. Clinically relevant drug-drug interactions have not been detected; however, limiting the dose to 2.5 mg once daily is recommended in the USA when saxagliptin is coadministered with strong CYP inhibitors, because of increased saxagliptin exposure. In summary, saxagliptin has a predictable pharmacokinetic and pharmacodynamic profile.

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Saxagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus

Cited by 12 publications

References 33 publications

STUDI IN SILICO POTENSI SENYAWA ALLIIN BAWANG PUTIH (Allium sativum) SEBAGAI INHIBITOR DPP-4 PADA DIABETES MELLITUS

STUDI IN SILICO POTENSI SENYAWA ALLIIN BAWANG PUTIH (Allium sativum) SEBAGAI INHIBITOR DPP-4 PADA DIABETES MELLITUS

Saxagliptin: A dipeptidyl peptidase-4 inhibitor in the treatment of type 2 diabetes mellitus

Clinical Pharmacokinetics and Pharmacodynamics of Saxagliptin, a Dipeptidyl Peptidase-4 Inhibitor

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